Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Department of Pediatrics and Pediatric Surgery, Intensive Care Erasmus MC-Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
European Journal of Intensive Care Medicine (Impact Factor: 5.54). 08/2009; 35(10):1754-60. DOI: 10.1007/s00134-009-1564-7
Source: PubMed

ABSTRACT Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO).
Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-(13)C] glucose. The (13)C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study.
Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 +/- 0.33 vs. 8.0 +/- 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 +/- 0.03 vs. 0.09 +/- 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 +/- 3.0 vs. 69.4 +/- 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups.
These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO.


Available from: Virgilio Paolo Carnielli, May 30, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: A diaphragmatic hernia is defined as the protrusion of abdominal viscera into the thoracic cavity through a normal or pathological orifice. The herniated viscera compress the lungs, resulting in pulmonary hypoplasia and secondary pulmonary hypertension, which are the leading causes of neonatal death in patients with congenital diaphragmatic hernia. Congenital diaphragmatic hernia is diagnosed by sonography in routine prenatal screening. Although magnetic resonance imaging is fundamentally used to determine whether the liver is located within the abdomen or has herniated into the thorax, it also can provide useful information about other herniated structures and the degree of pulmonary hypoplasia. The aim of this article is to review the fetal magnetic resonance findings for congenital diaphragmatic hernia and the signs that enable us to establish the neonatal prognosis when evaluating pulmonary hypoplasia.
    Radiología 03/2013; DOI:10.1016/j.rx.2012.12.003
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: There is no consensus or evidence as to whether a neuromuscular blocking agent should be used during the initial resuscitation of infants with congenital diaphragmatic hernia (CDH) in the labour ward. Objective: To determine if administration of a neuromuscular blocking agent affected the lung function of infants with CDH during their initial resuscitation in the labour ward. Methods: Fifteen infants with CDH were studied (median gestational age 38 weeks, range 34-41; birth weight 2,790 g, range 1,780-3,976). Six infants had undergone feto-endotracheal occlusion (FETO). Flow, airway pressure, tidal volume and dynamic lung compliance changes were recorded using a respiratory function monitor (NM3, Respironics). Twenty inflations immediately before, immediately after and 5 min after administration of a neuromuscular blocking agent (pancuronium bromide) were analysed. Results: The median dynamic lung compliance of the 15 infants was 0.22 ml/cm H(2)O/kg (range 0.1-0.4) before and 0.16 ml/cm H(2)O/kg (range 0.1-0.3) immediately after pancuronium bromide administration (p < 0.001) and remained at a similar low level 5 min after pancuronium bromide administration. The FETO compared to the non-FETO infants had a lower median dynamic compliance both before (p < 0.0001) and 5 min after pancuronium administration (p < 0.001) and required significantly longer durations of ventilation (p = 0.004), supplementary oxygen (p = 0.003) and hospitalisation (p = 0.007). Conclusions: Infants with CDH, particularly those who have undergone FETO, have a low lung compliance at birth, and this is further reduced by administration of a neuromuscular blocking agent.
    Neonatology 11/2012; 103(2):112-117. DOI:10.1159/000342332 · 2.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Surfactant therapy is one of the few treatments that have dramatically changed clinical practice in neonatology. In addition to respiratory distress syndrome (RDS), surfactant deficiency is observed in many other clinical situations in term and preterm infants, raising several questions regarding the use of surfactant therapy.Objectives: This review focuses on several points of interest, including some controversial or confusing topics being faced by clinicians together with emerging or innovative concepts and techniques, according to the state of the art and the published literature as of 2013. Surfactant therapy has primarily focused on RDS in the preterm newborn. However, whether this treatment would be of benefit to a more heterogeneous population of infants with lung diseases other than RDS needs to be determined. Early trials have highlighted the benefits of prophylactic surfactant administration to newborns judged to be at risk of developing RDS. In preterm newborns that have undergone prenatal lung maturation with steroids and early treatment with continuous positive airway pressure (CPAP), the criteria for surfactant administration, including the optimal time and the severity of RDS, are still under discussion. Tracheal intubation is no longer systematically done for surfactant administration to newborns. Alternative modes of surfactant administration, including minimally-invasive and aerosolized delivery, could thus allow this treatment to be used in cases of RDS in unstable preterm newborns, in whom the tracheal intubation procedure still poses an ethical and medical challenge. The optimization of the uses and methods of surfactant administration will be one of the most important challenges in neonatal intensive care in the years to come.
    BMC Pediatrics 10/2013; 13(1):165. DOI:10.1186/1471-2431-13-165 · 1.92 Impact Factor